Ceritinib: Indication, Pharmacology, Warnings, and Precautions

What Is Cerinitib?

Ceritinib is a medicine used to treat a type of lung cancer called non-small cell lung cancer (NSCLC). It works by targeting specific cancer cells. Ceritinib can be an important treatment option for some people with NSCLC, especially when other treatments do not work well or are no longer effective.

Is Cetritinib FDA-approved?

Ceritinib was approved by the U.S. Food and Drug Administration (FDA) in 2014 through a fast approval process because it showed promising results in treating lung cancer. This medicine is used for a specific type of non-small cell lung cancer (NSCLC) in patients whose cancer cells have a change in the ALK (anaplastic lymphoma kinase) gene. Ceritinib works by targeting the ALK protein in these cancer cells, helping slow or stop cancer growth.

For Patients:

How Does Ceritinib Work?

In some cases of non-small cell lung cancer (NSCLC), the cancer cells produce too much of the protein ALK (anaplastic lymphoma kinase) because of a mutation in the gene that encodes it. This extra ALK activity causes cells to grow and divide rapidly, leading to cancer.

Ceritinib works by targeting the ALK protein. It attaches to the protein and blocks its activity. By blocking ALK signaling, Ceritinib helps slow or stop the growth of cancer cells. Because of this, Ceritinib is used only for NSCLC patients whose cancer cells are ALK-positive.

What Is the Dosage of Ceritinib?

The usual recommended dose of Ceritinib is 750 milligrams (mg) per day, taken by mouth.

How Effective Is Ceritinib?

Ceritinib has shown good results in treating non-small cell lung cancer (NSCLC) that is caused by changes in the ALK gene. Studies and clinical trials have shown that the medicine can be effective and generally safe for many patients. Ceritinib can sometimes be more cost-effective than treatments like chemotherapy or Crizotinib, and it may also help improve a patient's life expectancy.

Usually, Crizotinib is the first-line treatment for ALK-positive NSCLC. However, its effect may decrease after about one year of treatment. When this happens, Ceritinib is often used as another treatment option. Some studies also suggest that Ceritinib may be effective even as the initial treatment for certain patients.

What Are the Things to Inform the Doctor Before Taking the Drug?

Before starting Ceritinib, patients should tell their doctor about the following:

• If they have ever had an allergy to Ceritinib before.

• If they have had allergic reactions to other medicines.

• All medicines they are currently taking, because Ceritinib can affect how other medicines work.

• If they use vitamins, herbal products, or other alternative medicines.

• Their current health conditions or other diseases.

• If they are pregnant or planning to become pregnant, Ceritinib should not be used during pregnancy.

• If they are breastfeeding, breastfeeding is not recommended while taking Ceritinib.

How Is Ceritinib Administered?

Ceritinib is taken by mouth as a capsule. The capsule should be swallowed whole with water and should not be chewed or crushed. It should not be taken with food because food can affect how the medicine works. Patients should usually take it one hour before a meal or two hours after eating. If a person vomits after taking the medicine, they should not take an extra dose. Instead, they should continue with the next scheduled dose as advised by their doctor.

What Are the Side Effects of Ceritinib?

Some possible side effects of Ceritinib include:

• Stomach discomfort.

• Stomach pain.

• Vomiting.

• Constipation.

• Heartburn (a burning-like feeling around the chest invoked upon eating).

• Weight loss.

• Diminished appetite.

• Troubled swallowing.

• Skin rash.

• Tiredness.

• Bone and muscle pain.

• Visual errors.

• Headache.

• Itching.

• Dark-colored urine.

• Yellowed skin.

• Breathlessness.

• Lightheadedness.

• Chest pain.

• Disordered heartbeat.

• Fainting.

• Depleted red cell count (anemia).

Dietary Considerations:

While taking Ceritinib, patients should avoid grapefruit and grapefruit juice. Grapefruit can increase the amount of the medicine in the blood, potentially causing side effects or toxicity.

Missed Dose:

If you miss a dose of Ceritinib, check how much time is left before your next dose.

• If the next dose is 12 hours or more away, take the missed dose as soon as you remember.

• If the next dose is less than 12 hours away, skip the missed dose and take the next dose at the usual time. Do not take two doses together.

Overdose:

Taking more than the recommended amount of Ceritinib can cause serious side effects. If an overdose happens, seek medical help immediately. Doctors usually treat the symptoms caused by the overdose.

Storage:

Keep the bottle tightly closed and store the medicine in the original container.

For Doctors:

Drug Group:

Ceritinib belongs to a group of medicines called tyrosine kinase inhibitors (TKIs).

Indications:

Non-small cell lung cancer (anaplastic lymphoma kinase positive).

Contraindications

Ceritinib allergy.

Dose:

The usual recommended dose of Ceritinib is 750 milligrams (mg) per day. However, the doctor may increase or decrease the dose depending on how well the patient responds to the medicine and tolerates it.

What Are the Pharmacological Aspects of Ceritinib?

Mechanism of Action:

• Ceritinib helps slow the progression of non-small cell lung cancer (NSCLC) by blocking the ALK (anaplastic lymphoma kinase) protein.

• In some people with NSCLC, changes in the ALK gene produce abnormal ALK proteins. These proteins send signals that drive cancer cells to grow and spread rapidly.

• Ceritinib binds to the ALK protein and inhibits its activity. This stops the signals that tell cancer cells to grow and divide.

• By blocking ALK and related signaling pathways, Ceritinib can slow the growth of cancer cells and may even cause some cancer cells to die, helping improve the patient’s chances of survival.

Pharmacodynamics:

In addition to its inhibitory action on ALK (anaplastic lymphoma kinase), Ceritinib can also affect and regulate the activity of several other proteins in the body. These proteins are involved in important cell signaling pathways that influence cell growth and survival. Some of the other biological targets that Ceritinib can act on include the insulin-like growth factor receptor 1 (IGF-1R), ROS1 (c-ROS proto-oncogene 1), and the insulin receptor (InsR). By influencing these proteins, Ceritinib may further help control abnormal signaling that contributes to cancer cell growth and progression.

Pharmacokinetics:

• After a person takes Ceritinib, the medicine usually reaches its peak blood level within about 4 to 6 hours. When Ceritinib is taken every day, it usually reaches a steady level in the blood after about 15 days.

• Taking Ceritinib with food can increase the amount of the drug absorbed in the body. Meals high in fat can increase this effect even more than low-fat meals.

• In the bloodstream, Ceritinib circulates by binding to plasma proteins. The medicine is mainly broken down in the liver by an enzyme called cytochrome P3A, although only a small portion of the drug is actually metabolized.

• Most of the Ceritinib is removed from the body through stool (feces), while a small amount is excreted in the urine.

Toxicity:

• Carcinogenicity: Ceritinib's carcinogenic properties have not been fully evaluated.

• Mutagenicity: The Ames test (a test to assess mutagens) did not detect mutagenicity with Ceritinib; however, it did identify aneugenic effects.

• Fertility Impairment: Fertility impairment has not been meticulously explored through studies.

Clinical Studies:

Discrete clinical studies were conducted for untreated and previously treated ALK-driven NSCLC patients.

Clinical Trial for Previously Untreated Subjects:

Ceritinib therapy demonstrated a significant improvement in progression-free survival compared with chemotherapy. The overall response rate with Ceritinib was estimated at 73 percent, compared with 27 percent with chemotherapy. Overall survival rates with Ceritinib are proportionate to those of chemotherapy.

Clinical Trial for Previously Treated Subjects:

The overall response rate with Ceritinib ranges from 43 to 55 percent. The trial results underscored the therapeutic relevance of Ceritinib as a viable option for Crizotinib-intolerant patient groups and demonstrated appreciable clinical benefits.

Warnings and Precautions:

• Liver Toxicity (Hepatotoxicity): Ceritinib can sometimes cause liver problems. It may increase liver enzyme levels such as alanine aminotransferase (ALT), alkaline phosphatase, and bilirubin. Higher levels of these enzymes can indicate liver damage. Because of this, doctors usually check liver function regularly during Ceritinib treatment.

• Lung Diseases: Ceritinib may rarely cause serious lung problems such as pneumonitis and interstitial lung disease. If these conditions occur, the medicine may need to be stopped immediately. Doctors usually monitor patients for symptoms like difficulty breathing or worsening cough during treatment.

• Bradycardia: Ceritinib can sometimes slow down the heart rate, a condition called bradycardia. In some cases, the heart rate may fall below 50 beats per minute. Lowering the dose of Ceritinib can often help reduce this problem.

• Gastrointestinal Toxicity: Many patients may experience stomach-related side effects while taking Ceritinib. These commonly include stomach pain, vomiting, and diarrhea.

• Prolonged QT Interval: Ceritinib can sometimes prolong the QT interval, a change in the heart’s electrical activity. This can increase the risk of serious heart rhythm problems such as ventricular tachyarrhythmia. People with existing heart conditions may have a higher risk, so doctors often monitor heart function during treatment.

• Hyperglycemia: Ceritinib may increase blood sugar levels, even in people without prior diabetes. Because of this, doctors may regularly check fasting blood sugar levels. If high blood sugar develops, doctors may adjust the Ceritinib dose or prescribe blood sugar-lowering medicines.

• Embryofetal Toxicity: Ceritinib can harm an unborn baby, so it is not recommended during pregnancy. Women taking Ceritinib should use effective birth control to avoid pregnancy. Men receiving Ceritinib are also advised to use contraception, such as condoms, because the medicine may affect reproductive cells.

• Pancreatitis: In rare cases, Ceritinib may cause pancreatitis, which is inflammation of the pancreas. This can happen when pancreatic enzymes such as lipase and amylase increase. Doctors may therefore monitor these enzyme levels regularly during Ceritinib therapy.

What Are the Drug Interactions of Ceritinib?

Here are some potential Ceritinib interactions:

With Strong Cytochrome P3A Inhibitors:

Some medicines can increase the level of Ceritinib in the blood by blocking the enzyme that normally breaks it down. These medicines are called strong CYP3A inhibitors.

When Ceritinib is taken with these drugs, the doctor may reduce the Ceritinib dose by about one-third to prevent side effects caused by high drug levels.

Examples of such medicines include Ketoconazole, Ritonavir, and Telithromycin.

With Strong Cytochrome P3A Inducers:

Some medicines can lower the amount of Ceritinib in the body by speeding its breakdown. These are called strong CYP3A inducers. When taken together, they may reduce the effectiveness of Ceritinib treatment.

Examples of these medicines include Phenytoin, Carbamazepine, and Rifampin.

Specific Considerations:

• Ceritinib During Pregnancy: Ceritinib can harm the unborn baby. It may interfere with the normal development of organs in the fetus and can increase the risk of birth defects or miscarriage. Because of this risk, pregnant women should not take Ceritinib.

• Ceritinib During Breastfeeding (Lactation): Ceritinib is not recommended for breastfeeding women. If a mother needs to take Ceritinib for medical reasons, breastfeeding should be stopped during the treatment and for at least two weeks after the therapy ends to make sure the medicine is no longer in the body.

• Ceritinib in Older Adults (Geriatric Population): Ceritinib generally works similarly in older adults and does not show major differences in effectiveness or safety compared to younger adults.

• Ceritinib in Children (Pediatric Population): The safety and effectiveness of Ceritinib have not been well studied in children, so it is not usually recommended for pediatric patients.